An Approach to the Core Structure of Leiodermatolide

Abstract

The synthesis of the 16-membered core structure of leiodermatolide 40 has been achieved in 26 linear steps starting from (R)-Roche ester. The key steps in the synthesis of 40 are a Stille cross-coupling between two main fragments 11 and 33 having roughly equal size. For the trisubstituted C4/C5 double bond a carbometalation reaction followed by a Suzuki coupling was used. A Yamaguchi macrolactonization furnished macrolactone 39.

Gold(I)‐, Palladium(II)‐, Platinum(II)‐, and Mercury(II)‐Catalysed Spirocyclization of 1,3‐Enynediols: Reaction Scope

“…Figure 1 shows the (Z)-vinyl bromides (i.e., 8a-8d) that were prepared and used in this study. Alkynol 5g [18] and protected alkynol 5d [19] were prepared as described in the literature. The yields for the individual steps leading to the vinyl bromides are listed in Table 1.…”

Divergent Total Synthesis of the Antimitotic Agent Leiodermatolide

“…[5] Approximately tenfold lower concentrations were detected in specimens harvested in the Bahamas, [7] whereas an earlier study on Leiodermatium sponges collected off Palau had only given structurally unrelated secondary metabolites of mixed polyketide/nonribosomal peptide synthetase origin ("leiotolides"). [5] However, the segregated stereoclusters within the macrolac-tone [10,11] and the d-lactone terminus could not be correlated with each other, thus leaving it open as to whether structure 1 or 2 represents the natural product (Scheme 1). [5] However, the segregated stereoclusters within the macrolac-tone [10,11] and the d-lactone terminus could not be correlated with each other, thus leaving it open as to whether structure 1 or 2 represents the natural product (Scheme 1).…”

Computer-Guided Total Synthesis of Natural Products. Recent Examples and Future Perspectives

“…Hence, the full configuration of leiodermatolide could only be solved by total synthesis, and it did not take long until the first studies began to appear. The first approach was carried out by Maier and co-workers 52 which synthesized the macrolide region of the natural product (78, Figure 20). Interestingly, the authors relied on an earlier preliminary structural proposal of leiodermatolide with an inverted configuration at C-6 and C-8.…”